1. Field of the Invention
The present invention relates generally to the treatment of rheumatoid arthritis. More particularly, the invention relates to the treatment of rheumatoid arthritis by oral administration of pooled human immunoglobulin.
2. Description of Related Art
The publications and other reference materials referred to herein to describe the background of the invention and to provide additional detail regarding its practice are hereby incorporated by reference.
Rheumatoid arthritis ("rheumatoid arthritis") is a systematic inflammatory disease that commonly affects the joints, particularly those of the hands and feet. The onset of rheumatoid arthritis can occur slowly, ranging from a few weeks to a few months, or the condition can surface rapidly in an acute manner.
Today, over 2,500,000 individuals are diagnosed with rheumatoid arthritis in the United States alone (1% of population), with some statistics indicating from 6.5 to 8 million potentially afflicted with the disease. Women are affected 2-3 times more often than men. The disease can occur at any age and typically will increase in incidence with age.
The classic early symptoms of rheumatoid arthritis include stiffness, tenderness, fever, subcutaneous nodules, achy joints, and fatigue. The joints of the hands, feet, knees and wrists are most commonly affected, with eventual involvement of the hips, elbows and shoulders. As the joints stiffen and swell, any type of motion becomes very painful and difficult. The more severe cases of rheumatoid arthritis can lead to intense pain and eventual joint destruction. Some 300,000 bone and joint replacement surgical procedures are performed annually in an effort to alleviate the pain and mobility loss resultant from arthritis related joint destruction.
The effective treatment of rheumatoid arthritis has generally comprised a combination of medication, exercise, rest and proper joint protection therapy. The therapy for a particular patient depends on the severity of the disease and the joints that are involved. Aspirin is widely used for pain and to reduce inflammation. In addition to aspirin, non-steroidal anti-inflammatory drugs, corti-costeroids, gold salts, anti-malarials and systemic immunosuppressants are widely used in moderate to advanced cases. The use of steroids and immunosuppressants, however, has significant risks and side effects both in terms of toxicity and vulnerability to potentially lethal conditions. There, thus exists a need for a method of treating rheumatoid arthritis which does not entail the potentially lethal side effects associated with the treatments described above.
"Superantigens" have been considered as stimulants of the immune system in various autoimmune diseases including rheumatoid arthritis. Herman, A., et al. (1991) Annu. Rev. Immunol. 9:745-772; Drake, C. G. and Kotzin, B. L. (1992) J. Clin. Immunol. 12:149-162. The gastrointestinal tract may be the site of immunologic stimulation by superantigens. There may be a defect in the ability of patients with rheumatoid arthritis to produce antibodies with the correct neutralizing specificities. One approach to treating rheumatoid arthritis is to orally administer cow's milk to patients. See U.S. Pat. No. 4,732,757 (Stolle et al.). Therein it is disclosed that rheumatoid arthritis may be treated by the oral administration of cow's milk, the milk containing IgGs against a large group of bacteria with which the producing cow was vaccinated. The drawbacks to this approach are twofold. First, some patients have adverse reactions to consumption of bovine milk; second, cow's milk does not contain the entire spectrum of antibodies present in a human.
A second approach to the treatment of autoimmune diseases, of which rheumatoid arthritis is an example, is tolerazation of the patient suffering from the autoimmune disease to the particular autoantigen(s) involved in the disease. In Weiner et al., Science 259:1321-1324 (1993), multiple sclerosis patients were orally administered bovine myelin protein, which contains two of the diseases autoantigens. In Trentham et al., Science 261:1727-1730 (1993), rheumatoid arthritis patients were orally administered collagen, a presumed autoantigen. The drawback to tolerazation is identification of the correct autoantigen to which tolerance is to be induced.
In view of the above there is a continued need to develop methods for the treatment of rheumatoid arthritis.